Synthesis of tyrosine aminotransferase in rat liver is limited and insensitive to control by glucocorticoids during fetal life; within a few hours after birth, capacity to synthesize the enzyme and glucocorticoid sensitivity are developed. This change also occurs in fetal livers placed in organ culture. This model of a rapid and well-defined enzymic differentiation in mammalian cells will be analyzed in detail to determine the molecular mechanism involved and the factors controlling it. Perinatal changes in functional mRNA will be determined by translation assay, and the synthesis and processing of total mRNA transcripts by hybridization to specific cDNA. Changes in rate of transcription of the structural gene will be measured in organ or cell cultures of fetal hepatocytes. When the cellular mechanism involved in the differentiation process is identified, the developmental shift will be defined in terms of molecular interactions. Factors of the intrauterine environment operative in prenatal repression of aminotransferase will be sought and their mode of operation analyzed.